Search

Abstract Background Size of the reference population and reliability of phenotypes are crucial factors influencing the reliability of genomic predictions. It is therefore useful to combine closely related populations. Increased accuracies of genomic predictions depend on the number of individuals added to the reference population, the reliability of their phenotypes, and the relatedness of the populations that are combined. Methods This paper assesses the increase in reliability achieved when combining four Holstein reference populations of 4000 bulls each, from European breeding organizations, i.e. UNCEIA (France), VikingGenetics (Denmark, Sweden, Finland), DHV-VIT (Germany) and CRV (The Netherlands, Flanders). Each partner validated its own bulls using their national reference data and the combined data, respectively. Results Combining the data significantly increased the reliability of genomic predictions for bulls in all four populations. Reliabilities increased by 10%, compared to reliabilities obtained with national reference populations alone, when they were averaged over countries and the traits evaluated. For different traits and countries, the increase in reliability ranged from 2% to 19%. Conclusions Genomic selection programs benefit greatly from combining data from several closely related populations into a single large reference population.

Computer-based analysis of long-term electrocardiogram (ECG) monitoring in animal models represents a cost and time-consuming process as manual supervision is often performed to ensure accuracy in arrhythmia detection. Here, we investigate the performance and feasibility of three ECG interval analysis approaches A) attribute-based, B) attribute- and pattern recognition-based and C) combined approach with additional manual beat-to-beat analysis (gold standard) with regard to subsequent detection of ventricular arrhythmias (VA) and time consumption. ECG analysis was performed on ECG raw data of 5 male cynomolgus monkeys (1000 h total, 2 × 100 h per animal). Both approaches A and B overestimated the total number of arrhythmias compared to gold standard (+8.92% vs. +6.47%). With regard to correct classification of detected VA event numbers (accelerated idioventricular rhythms [AIVR], ventricular tachycardia [VT]) approach B revealed higher accuracy compared to approach A. Importantly, VA burden (% of time) was precisely depicted when using approach B (-1.13%), whereas approach A resulted in relevant undersensing of ventricular arrhythmias (-11.76%). Of note, approach A and B could be performed with significant less working time (-95% and - 91% working time) compared to gold standard. In sum, we show that a combination of attribute-based and pattern recognition analysis (approach B) can reproduce VA burden with acceptable accuracy without using manual supervision. Since this approach allowed analyses to be performed with distinct time saving it represents a valuable approach for cost and time efficient analysis of large preclinical ECG datasets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Concerns exist regarding effects of puberty suppression on neurodevelopment. Intelligence is strongly correlated with educational achievement in the general population. This study aimed to examine the association between pre-treatment intelligence and educational achievement after gender-affirming treatment including puberty suppression in transgender adolescents to contribute to the emerging understanding of the effect that gender-affirming treatment including puberty suppression may have on cognitive development., Methods: IQ was measured in 72 adolescents (45 trans boys, 27 trans girls) at clinical entry (mean age 12.78 years), educational achievement was evaluated after gender-affirming treatment (mean age 20.40 years)., Results: IQ pre-treatment and educational achievement post-treatment were positively associated (Nagelkerke R = 0.71)., Discussion: The association between IQ pre-treatment and educational achievement post-treatment in transgender adolescents who received gender-affirming medical treatment including puberty suppression appears to be similar to the general population. This may reflect that gender-affirming medical treatment including puberty suppression does not negatively affect the association between IQ and educational achievement.

Transgender children and adolescents show high rates of co-occurring psychopathology, which might be related to low self-confidence. Earlier research showed that compared to the norm population, transgender clinic-referred children have lower self-perception on two domains: physical appearance and global self-worth. This study aimed to compare self-perception in a sample of transgender clinic-referred children and adolescents with their standardization samples and to examine differences between these two groups. To measure self-esteem, the Self-Perception Profile for Children was administered to 305 referred children (162 assigned males at birth (AMABs) and 143 assigned females at birth (AFABs), mean age = 9.05 ( SD, 1.47), range = 5.9-13.00 years), and the Self-Perception Profile for Adolescents was administered to 369 referred adolescents (118 AMABs and 251 AFABs, mean age = 15.27 ( SD, 1.80), range = 10.73-18.03 years). To measure the severity of gender dysphoria, the parents of the children completed the Gender Identity Questionnaire and the adolescents completed the Utrecht Gender Dysphoria Scale. Referred children and adolescents had a significantly lower self-concept compared to the normative population, whereby referred adolescents felt less competent compared to referred children. Compared to their peers, childhood referred AFABs perceived themselves even better on scholastic and athletic competence and social acceptance. With regard to gender differences, referred AFABs generally showed a better self-perception compared to referred AMABs. The lower self-perception of transgender clinic-referred children and adolescents compared to same age peers deserves clinical attention and interventions aimed at, for example, improving social and physical self-worth.

Purpose: Controversy exists as to if, and when, gender affirmative (GA) treatment should be offered to individuals with gender dysphoria (GD) and co-existing psychosis. Concerns exist regarding a high risk of misdiagnosis, regret afterward due to impulsive decision making, and deterioration of psychotic symptoms. This case series aims at extending the sparse literature on GA treatment in this population by identifying challenges in diagnosis and treatment and offering recommendations to overcome them., Case Series: The authors present case descriptions of two transgender men and two transgender women in the age range of 29-57 years with a diagnosis of GD and a schizophrenia-related diagnosis. All had undergone GA treatment with a minimum follow-up of 3 years. The gender diagnosis was complicated by the fact that feelings of GD were only shared after the onset of psychosis, and GA treatment was hampered by the persistence of mild psychotic symptoms despite antipsychotic treatment. Close communication with the psychosis treating clinicians proved useful to address these problems. GA treatment was paralleled by a stabilization of psychotic symptoms, and adherence to and satisfaction with the therapy was high., Conclusion: These case examples show that GA treatment is possible and safe in this vulnerable population.

The World Health Organization (WHO) is revising the tenth version of the International Classification of Diseases and Related Health Problems (ICD-10). This includes a reconceptualization of the definition and positioning of Gender Incongruence of Childhood (GIC). This study aimed to: 1) collect the views of transgender individuals and professionals regarding the retention of the diagnosis; 2) see if the proposed GIC criteria were acceptable to transgender individuals and health care providers; 3) compare results between two countries with two different healthcare systems to see if these differences influence opinions regarding the GIC diagnosis; and 4) determine whether healthcare providers from high-income countries feel that the proposed criteria are clinically useful and easy to use. A total of 628 participants were included in the study: 284 from the Netherlands (NL; 45.2%), 8 from Flanders (Belgium; 1.3%), and 336 (53.5%) from the United Kingdom (UK). Most participants were transgender people (or their partners/relatives; TG) (n = 522), 89 participants were healthcare providers (HCPs) and 17 were both HCP and TG individuals. Participants completed an online survey developed for this study. Overall, the majority response from transgender participants (42.9%) was that if the diagnosis would be removed from the mental health chapter it should also be removed from the ICD-11 completely, while 33.6% thought it should remain in the ICD-11. Participants were generally satisfied with other aspects of the proposed ICD-11 GIC diagnosis: most TG participants (58.4%) thought the term Gender Identity Disorder should change, and most thought Gender Incongruence was an improvement (63.0%). Furthermore, most participants (76.1%) did not consider GIC to be a psychiatric disorder and placement in a separate chapter dealing with Gender and Sexual Health (the majority response in the NL and selected by 37.5% of the TG participants overall) or as a Z-code (the majority response in the UK and selected by 26.7% of the TG participants overall) would be preferable. In the UK, the majority response (35.8%) was that narrowing the GIC diagnosis was an improvement, while the NL majority response (49.5%) was that this was not an improvement. Although generally the results from HCPs were in line with the results from TG participants some differences were found. This study suggests that, although in an ideal world a diagnosis is not welcomed, several participants felt the diagnosis should not be removed. This is likely due to concerns about restricting access to reimbursed healthcare. The choice for positioning of a diagnosis of GIC within the ICD-11 was as a separate chapter dealing with symptoms and/or disorders regarding sexual and gender health. This was the overall first choice for NL participants and second choice for UK participants, after the use of a Z-code. The difference reflects that in the UK, Z-codes carry no negative implications for reimbursement of treatment costs. These findings highlight the challenges faced by the WHO in their attempt to integrate research findings from different countries, with different cultures and healthcare systems in their quest to create a manual that is globally applicable., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Professor Peggy Cohen-Kettenis is a member of the Working Group on the Classification of Sexual Disorders and Sexual Health (WGSDSH) of the World Health Organization. The WGSDSH has developed the diagnostic criteria for Gender Incongruence and advised regarding its placement in the ICD-11. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The recognition and acknowledgment that gender identity and birth-assigned sex may be incongruent in children and adolescents have evolved in recent decades. Transgender care for children and adolescents has developed and is now more widely available. Controversies exist, however, around clinical management of gender dysphoria and gender incongruence in children and adolescents. Clinical guidelines are consensus based and research evidence is limited. Puberty suppression as part of clinical management has become a valuable element of adolescent transgender care, but long-term evidence of success is limited. These uncertainties should be weighed against the risk of harming a transgender adolescent when medical intervention is denied., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The World Health Organization (WHO) is currently updating the tenth version of their diagnostic tool, the International Classification of Diseases (ICD, WHO, 1992). Changes have been proposed for the diagnosis of Transsexualism (ICD-10) with regard to terminology, placement and content. The aim of this study was to gather the opinions of transgender individuals (and their relatives/partners) and clinicians in the Netherlands, Flanders (Belgium) and the United Kingdom regarding the proposed changes and the clinical applicability and utility of the ICD-11 criteria of 'Gender Incongruence of Adolescence and Adulthood' (GIAA). A total of 628 participants were included in the study: 284 from the Netherlands (45.2%), 8 from Flanders (Belgium) (1.3%), and 336 (53.5%) from the UK. Most participants were transgender people (or their partners/relatives) (n = 522), 89 participants were healthcare providers (HCPs) and 17 were both healthcare providers and (partners/relatives of) transgender people. Participants completed an online survey developed for this study. Most participants were in favor of the proposed diagnostic term of 'Gender Incongruence' and thought that this was an improvement on the ICD-10 diagnostic term of 'Transsexualism'. Placement in a separate chapter dealing with Sexual- and Gender-related Health or as a Z-code was preferred by many and only a small number of participants stated that this diagnosis should be excluded from the ICD-11. In the UK, most transgender participants thought there should be a diagnosis related to being trans. However, if it were to be removed from the chapter on "psychiatric disorders", many transgender respondents indicated that they would prefer it to be removed from the ICD in its entirety. There were no large differences between the responses of the transgender participants (or their partners and relatives) and HCPs. HCPs were generally positive about the GIAA diagnosis; most thought the diagnosis was clearly defined and easy to use in their practice or work. The duration of gender incongruence (several months) was seen by many as too short and required a clearer definition. If the new diagnostic term of GIAA is retained, it should not be stigmatizing to individuals. Moving this diagnosis away from the mental and behavioral chapter was generally supported. Access to healthcare was one area where retaining a diagnosis seemed to be of benefit., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Professor Peggy Cohen-Kettenis is a member of the Working Group on the Classification of Sexual Disorders and Sexual Health (WGSDSH) of the World Health Organization. The WGSDSH has developed the diagnostic criteria for Gender Incongruence and advised regarding its placement in the ICD-11. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Disorders of attachment and social engagement have mainly been studied in children, reared in institutions and foster care. There are few studies amongst home reared children living with biological parents. The aim of this study was to test the clinical significance of inhibited attachment behaviour and disinhibited social engagement behaviour in young home reared children, referred for treatment of emotional and behavioural problems, compared with young children in treatment foster care., Methods: The Disturbances of Attachment Interview, Maltreatment Classification System, the Child Behaviour Checklist and Parenting Stress Index were used in 141 referred home reared children and 59 referred foster children, aged 2.0-7.9 years (M = 4.7, SE = 1.3), 71% boys., Results: Inhibited attachment behaviour was less prevalent in the referred home reared group (9%) than in the foster care group (27%). Disinhibited social engagement behaviour was found in 42% of the home reared group, similar to the foster care group. Inhibited attachment behaviour and disinhibited social engagement behaviour were not associated with child maltreatment. More inhibited attachment behaviour was associated with clinical levels of child internalizing and externalizing behaviour in the home reared group, not in the foster care group. In both groups, more disinhibited social engagement behaviour was associated with clinical levels of externalizing behaviour and with more parenting stress., Conclusions: Even without evident links to maltreatment, results of this study suggest clinical significance of inhibited attachment behaviour and disinhibited social engagement behaviour in young home reared children referred for treatment of emotional and behavioural problems., (© 2016 John Wiley & Sons Ltd.)

This study is the third in a series to examine behavioral and emotional problems in children and adolescents with gender dysphoria in a comparative analysis between two clinics in Toronto, Ontario, Canada and Amsterdam, the Netherlands. In the present study, we report Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) data on adolescents assessed in the Toronto clinic (n = 177) and the Amsterdam clinic (n = 139). On the CBCL and the YSR, we found that the percentage of adolescents with clinical range behavioral and emotional problems was higher when compared to the non-referred standardization samples but similar to the referred adolescents. On both the CBCL and the YSR, the Toronto adolescents had a significantly higher Total Problem score than the Amsterdam adolescents. Like our earlier studies of CBCL data of children and Teacher's Report Form data of children and adolescents, a measure of poor peer relations was the strongest predictor of CBCL and YSR behavioral and emotional problems in gender dysphoric adolescents.

The current literature shows growing evidence of a link between gender dysphoria (GD) and autism spectrum disorder (ASD). This study reviews the available clinical and empirical data. A systematic search of the literature was conducted using the following databases: PubMed, Web of Science, PsycINFO and Scopus; utilizing different combinations of the following search terms: autism, autism spectrum disorder (ASD), Asperger's disorder (AD), co-morbidity, gender dysphoria (GD), gender identity disorder (GID), transgenderism and transsexualism. In total, 25 articles and reports were selected and discussed. Information was grouped by found co-occurrence rates, underlying hypotheses and implications for diagnosis and treatment. GD and ASD were found to co-occur frequently - sometimes characterized by atypical presentation of GD, which makes a correct diagnosis and determination of treatment options for GD difficult. Despite these challenges there are several case reports describing gender affirming treatment of co-occurring GD in adolescents and adults with ASD. Various underlying hypotheses for the link between GD and ASD were suggested, but almost all of them lack evidence.

Adolescents presenting with gender-related concerns are increasingly seeking support from providers from a variety of disciplines within health care settings across the world. For those treating young people who meet the criteria for the DSM 5 diagnosis of gender dysphoria (GD), complex decisions in clinical care are common. Defining best practice with this population with respect to interventions that span mental health, physical, and surgical domains can be challenging, given a relative dearth of empirical data available; yet practice guidelines have emerged from different professional organizations which can aid with this. For this review paper, a broad literature search was performed to identify relevant studies pertaining to the care of adolescents with GD. In addition, an overview of trends in clinical practice, including shifts in conceptualization of how clinicians and patients define care that is considered affirming when working with this population, is described. This paper explores the characteristics of referral patterns to specialized clinics, provides a brief overview of gender identity development in adolescence, and then describes the phenomenology of known aetiological factors and co-occurring psychiatric issues in adolescents with GD. Additionally, clinical management considerations that detail assessment aims and common treatment interventions across disciplines will be explored.

Introduction: The number of adolescents referred to specialized gender identity clinics for gender dysphoria appears to be increasing and there also appears to be a corresponding shift in the sex ratio, from one favoring natal males to one favoring natal females., Aim: We conducted two quantitative studies to ascertain whether there has been a recent inversion of the sex ratio of adolescents referred for gender dysphoria., Methods: The sex ratio of adolescents from two specialized gender identity clinics was examined as a function of two cohort periods (2006-2013 vs. prior years). Study 1 was conducted on patients from a clinic in Toronto, and Study 2 was conducted on patients from a clinic in Amsterdam., Results: Across both clinics, the total sample size was 748. In both clinics, there was a significant change in the sex ratio of referred adolescents between the two cohort periods: between 2006 and 2013, the sex ratio favored natal females, but in the prior years, the sex ratio favored natal males. In Study 1 from Toronto, there was no corresponding change in the sex ratio of 6,592 adolescents referred for other clinical problems., Conclusions: Sociological and sociocultural explanations are offered to account for this recent inversion in the sex ratio of adolescents with gender dysphoria., (© 2015 International Society for Sexual Medicine.)

Background: In recent years, puberty suppression by means of gonadotropin-releasing hormone analogs has become accepted in clinical management of adolescents who have gender dysphoria (GD). The current study is the first longer-term longitudinal evaluation of the effectiveness of this approach., Methods: A total of 55 young transgender adults (22 transwomen and 33 transmen) who had received puberty suppression during adolescence were assessed 3 times: before the start of puberty suppression (mean age, 13.6 years), when cross-sex hormones were introduced (mean age, 16.7 years), and at least 1 year after gender reassignment surgery (mean age, 20.7 years). Psychological functioning (GD, body image, global functioning, depression, anxiety, emotional and behavioral problems) and objective (social and educational/professional functioning) and subjective (quality of life, satisfaction with life and happiness) well-being were investigated., Results: After gender reassignment, in young adulthood, the GD was alleviated and psychological functioning had steadily improved. Well-being was similar to or better than same-age young adults from the general population. Improvements in psychological functioning were positively correlated with postsurgical subjective well-being., Conclusions: A clinical protocol of a multidisciplinary team with mental health professionals, physicians, and surgeons, including puberty suppression, followed by cross-sex hormones and gender reassignment surgery, provides gender dysphoric youth who seek gender reassignment from early puberty on, the opportunity to develop into well-functioning young adults., (Copyright © 2014 by the American Academy of Pediatrics.)

Background: The Internet is used increasingly for both suicide research and prevention. To optimize online assessment of suicidal patients, there is a need for short, good-quality tools to assess elevated risk of future suicidal behavior. Computer adaptive testing (CAT) can be used to reduce response burden and improve accuracy, and make the available pencil-and-paper tools more appropriate for online administration., Objective: The aim was to test whether an item response-based computer adaptive simulation can be used to reduce the length of the Beck Scale for Suicide Ideation (BSS)., Methods: The data used for our simulation was obtained from a large multicenter trial from The Netherlands: the Professionals in Training to STOP suicide (PITSTOP suicide) study. We applied a principal components analysis (PCA), confirmatory factor analysis (CFA), a graded response model (GRM), and simulated a CAT., Results: The scores of 505 patients were analyzed. Psychometric analyses showed the questionnaire to be unidimensional with good internal consistency. The computer adaptive simulation showed that for the estimation of elevation of risk of future suicidal behavior 4 items (instead of the full 19) were sufficient, on average., Conclusions: This study demonstrated that CAT can be applied successfully to reduce the length of the Dutch version of the BSS. We argue that the use of CAT can improve the accuracy and the response burden when assessing the risk of future suicidal behavior online. Because CAT can be daunting for clinicians and applied scientists, we offer a concrete example of our computer adaptive simulation of the Dutch version of the BSS at the end of the paper.

This article is part of a Special Issue "Puberty and Adolescence".This article aims to provide an outline of what is currently known on trajectories, and contributing factors to gender identity development in adolescence. We give a historical overview of the concept of gender identity, and describe general identity development in adolescence, gender identity development in the general population and in gender variant youth. Possible psychosocial (such as child and parental characteristics) and biological factors (such as the effects of prenatal exposure to gonadal hormones and the role of genetics) contributing to a gender variant identity are discussed. Studies focusing on a number of psychosocial and biological factors separately, indicate that each of these factors influence gender identity formation, but little is known about the complex interplay between the factors, nor about the way individuals themselves contribute to the process. Research into normative and gender variant identity development of adolescents is clearly lagging behind. However, studies on persons with gender dysphoria and disorders of sex development, show that the period of adolescence, with its changing social environment and the onset of physical puberty, seems to be crucial for the development of a non-normative gender identity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Self-sampling for high-risk human papillomavirus (hrHPV) testing is accepted by up to 30% of non-attendees to the regular cervical screening programme. Here, the yield of cervical intraepithelial neoplasia (CIN)2 or worse (≥ CIN2) and CIN3 or worse (≥ CIN3) of 15, 274 HPV self-sampling responders amongst non-attendees were compared to that of 176, 027 women participating in regular screening in the same period and in the same region. We also analysed which subpopulations amongst non-attendees are targeted by HPV self-sampling, and which characteristics relate to hrHPV prevalence and yield of ≥ CIN2/≥ CIN3., Method: Data from two consecutive self-sampling studies were pooled. ≥ CIN2/≥ CIN3 yields, screening history, age and ethnic status were retrieved from centralised pathology and screening databases, respectively. A logistic regression model was fitted to analyse method of invitation, ethnicity, age group, and screening history as predictors for response rate, hrHPV presence and ≥ CIN2/≥ CIN3 in non-attendees. For screening history analyses, women < 34 years were excluded since it was the first screening round in their life., Findings: ≥ CIN2/≥ CIN3 yields of HPV self-sampling responders were higher than those of screening participants (≥ CIN2: relative risk (RR) = 1.6, 95% confidence interval = 1.4-1.9; ≥ CIN3: RR = 1.8, 95%CI = 1.5-2.1 with relative risk values increasing with age (test of homogeneity:≥ CIN2: p = 0.04; ≥ CIN3: p=0.03). Native Dutch non-attendees responded better than immigrants (32% versus 22%, p<0.001) and those screened in the previous round revealed a higher response than underscreened (i.e. previous smear taken >7 years ago) or never screened (34% versus 25%, p<0.001) women. Strikingly, amongst under- and never screened women aged ≥ 39 years, never screened women responded better (25% versus 23%, p<0.001). ≥ CIN2 rates were higher amongst responding native Dutch women than immigrants (p<0.01), and higher in under-/never screened women than in women screened in the previous round (p<0.01)., Interpretation: Offering hrHPV self-sampling increases the efficacy of the screening programme by targeting a substantial portion of non-attendees of all ethnic groups who have not regularly been screened and are at highest risk of ≥ CIN2., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Currently, women treated for high-grade cervical intraepithelial neoplasia (CIN 2/3) are followed-up by cytology to monitor them for residual and recurrent (post-treatment) disease. This systematic review and meta-analysis determine the test performance of testing for high-risk types of the human papillomavirus (hrHPV), cytology and co-testing (combined hrHPV testing and cytology) in predicting high-grade post-treatment disease (CIN2+)., Methods: Studies that compared at least two of three post-treatment surveillance methods, and were published between January 2003 and May 2011, were identified through a bibliographic database search (PubMed, Embase.com and Wiley/Cochrane Library). Identification of relevant studies was conducted independently by two reviewers with a multi-step process. The reference standard used to diagnose post-treatment disease was histologically confirmed CIN2+. Sensitivity, specificity, diagnostic odds ratios and relative sensitivity and specificity were calculated for each study. Pooled estimates were calculated using a random effects model if heterogeneity among studies was significant, otherwise by using a fixed effects model. Estimates were reported with 95% confidence intervals (95%CI)., Results: Out of 2410 potentially relevant citations, 8 publications, incorporating 1513 treated women, were included. Pooled sensitivities were 0.79 (95%CI 0.72-0.85) for cytology, 0.92 (0.87-0.96) for hrHPV testing, and 0.95 (0.91-0.98) for co-testing. HrHPV testing was more sensitive than cytology to predict post-treatment CIN2+ (relative sensitivity 1.15; 95%CI 1.06-1.25). Pooled specificities were 0.81 (95%CI 0.74-0.86) for cytology, 0.76 (0.67-0.84) for hrHPV testing and 0.67 (0.60-0.74) for co-testing. HrHPV testing and cytology had a similar specificity (relative specificity 0.95, 95%CI 0.88-1.02)., Conclusions: This review indicates that the hrHPV test should be included in post-treatment testing 6months after treatment, because hrHPV testing has a higher sensitivity than cytology in detecting high-grade post-treatment disease and has a similar specificity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The Dutch approach on clinical management of both prepubertal children under the age of 12 and adolescents starting at age 12 with gender dysphoria, starts with a thorough assessment of any vulnerable aspects of the youth's functioning or circumstances and, when necessary, appropriate intervention. In children with gender dysphoria only, the general recommendation is watchful waiting and carefully observing how gender dysphoria develops in the first stages of puberty. Gender dysphoric adolescents can be considered eligible for puberty suppression and subsequent cross-sex hormones when they reach the age of 16 years. Currently, withholding physical medical interventions in these cases seems more harmful to wellbeing in both adolescence and adulthood when compared to cases where physical medical interventions were provided.

Background: This study examined psychiatric comorbidity in adolescents with a gender identity disorder (GID). We focused on its relation to gender, type of GID diagnosis and eligibility for medical interventions (puberty suppression and cross-sex hormones)., Methods: To ascertain DSM-IV diagnoses, the Diagnostic Interview Schedule for Children (DISC) was administered to parents of 105 gender dysphoric adolescents., Results: 67.6% had no concurrent psychiatric disorder. Anxiety disorders occurred in 21%, mood disorders in 12.4% and disruptive disorders in 11.4% of the adolescents. Compared with natal females (n = 52), natal males (n = 53) suffered more often from two or more comorbid diagnoses (22.6% vs. 7.7%, p = .03), mood disorders (20.8% vs. 3.8%, p = .008) and social anxiety disorder (15.1% vs. 3.8%, p = .049). Adolescents with GID considered to be 'delayed eligible' for medical treatment were older [15.6 years (SD = 1.6) vs. 14.1 years (SD = 2.2), p = .001], their intelligence was lower [91.6 (SD = 12.4) vs. 99.1 (SD = 12.8), p = .011] and a lower percentage was living with both parents (23% vs. 64%, p < .001). Although the two groups did not differ in the prevalence of psychiatric comorbidity, the respective odds ratios ('delayed eligible' adolescents vs. 'immediately eligible' adolescents) were >1.0 for all psychiatric diagnoses except specific phobia., Conclusions: Despite the suffering resulting from the incongruence between experienced and assigned gender at the start of puberty, the majority of gender dysphoric adolescents do not have co-occurring psychiatric problems. Delayed eligibility for medical interventions is associated with psychiatric comorbidity although other factors are of importance as well., (© 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.)

In the Netherlands, gender dysphoric adolescents may be eligible for puberty suppression at age 12, subsequent cross-sex hormone treatment at age 16, and gender reassignment surgery at age 18. Initially, a thorough assessment is made of the gender dysphoria and vulnerabilities in functioning or circumstances. Psychological interventions and/or gender reassignment may be offered. Psychological interventions are offered if the adolescent needs to explore gender identity and treatment wishes, suffers from coexisting problems, or needs support and counseling during gender reassignment. Although more studies are necessary, this approach seems to contribute significantly to the well-being of gender dysphoric adolescents.

Puberty suppression by means of gonadotropin releasing hormone (GnRH) analogs is considered a diagnostic aid in gender dysphoric adolescents. However, there are also concerns about potential risks, such as poor outcome or post-surgical regret, adverse effects on metabolic and endocrine status, impaired increment of bone mass, and interference with brain development. This case report is on a 22-year follow-up of a female-to-male transsexual, treated with GnRH analogs at 13 years of age and considered eligible for androgen treatment at age 17, and who had gender reassignment surgery at 20 and 22 years of age. At follow-up, he indicated no regrets about his treatment. He was functioning well psychologically, intellectually, and socially; however, he experienced some feelings of sadness about choices he had made in a long-lasting intimate relationship. There were no clinical signs of a negative impact on brain development. He was physically in good health, and metabolic and endocrine parameters were within reference ranges. Bone mineral density was within the normal range for both sexes. His final height was short as compared to Dutch males; however, his body proportions were within normal range. This first report on long-term effects of puberty suppression suggests that negative side effects are limited and that it can be a useful additional tool in the diagnosis and treatment of gender dysphoric adolescents.

Introduction: Puberty suppression by means of gonadotropin-releasing hormone analogues (GnRHa) is used for young transsexuals between 12 and 16 years of age. The purpose of this intervention is to relieve the suffering caused by the development of secondary sex characteristics and to provide time to make a balanced decision regarding actual gender reassignment., Aim: To compare psychological functioning and gender dysphoria before and after puberty suppression in gender dysphoric adolescents., Methods: Of the first 70 eligible candidates who received puberty suppression between 2000 and 2008, psychological functioning and gender dysphoria were assessed twice: at T0, when attending the gender identity clinic, before the start of GnRHa; and at T1, shortly before the start of cross-sex hormone treatment., Main Outcome Measures: Behavioral and emotional problems (Child Behavior Checklist and the Youth-Self Report), depressive symptoms (Beck Depression Inventory), anxiety and anger (the Spielberger Trait Anxiety and Anger Scales), general functioning (the clinician's rated Children's Global Assessment Scale), gender dysphoria (the Utrecht Gender Dysphoria Scale), and body satisfaction (the Body Image Scale) were assessed., Results: Behavioral and emotional problems and depressive symptoms decreased, while general functioning improved significantly during puberty suppression. Feelings of anxiety and anger did not change between T0 and T1. While changes over time were equal for both sexes, compared with natal males, natal females were older when they started puberty suppression and showed more problem behavior at both T0 and T1. Gender dysphoria and body satisfaction did not change between T0 and T1. No adolescent withdrew from puberty suppression, and all started cross-sex hormone treatment, the first step of actual gender reassignment., Conclusion: Puberty suppression may be considered a valuable contribution in the clinical management of gender dysphoria in adolescents., (© 2010 International Society for Sexual Medicine.)

Sex, sexual orientation and age have been shown to be important in relation to psychological functioning in transsexuals. However, only few studies to date took these factors into account and not earlier have adolescent transsexuals participated. In this study the Minnesota Multiphasic Personality Inventory (MMPI-2 or MMPI-A, respectively) was administered to 293 adults (207 male to female transsexuals (MtFs), mean age 38.04 (range 18.56-65.62) and 86 female to male transsexuals (FtMs), mean age 33.26 (range 18.95-64.30)) and 83 adolescents (43 MtFs, mean age 15.70 (range 13.16-18.70) and 40 FtMs, mean age 15.64 (range 13.05-18.56)) with a gender identity disorder (GID). Of adult MtFs, 33% were categorized as "homosexuals" and 66% as "non-homosexuals". Of adult FtMs, 77% were categorized as "homosexuals" and 33% as "non-homosexuals". Adult FtMs functioned significantly better than MtFs on three clinical scales. Contrary to what is often assumed, no differences in psychological functioning were found in the adult transsexuals with regard to sexual orientation, except on one clinical scale. Most remarkably, significantly more adults with GID scored in the clinical range on two or more clinical scales than adolescents with GID. Therefore, early medical intervention may be recommendable for adolescents with GID., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Only case reports have described the co-occurrence of gender identity disorder (GID) and autism spectrum disorders (ASD). This study examined this co-occurrence using a systematic approach. Children and adolescents (115 boys and 89 girls, mean age 10.8, SD = 3.58) referred to a gender identity clinic received a standardized assessment during which a GID diagnosis was made and ASD suspected cases were identified. The Dutch version of the Diagnostic Interview for Social and Communication Disorders (10th rev., DISCO-10) was administered to ascertain ASD classifications. The incidence of ASD in this sample of children and adolescents was 7.8% (n = 16). Clinicians should be aware of co-occurring ASD and GID and the challenges it generates in clinical management.

This article reviews studies on gender identity outcome in individuals with disorders of sex development (DSD). It appears that a high percentage of affected individuals suffer from gender dysphoria. However, these figures differ substantially among the various DSD and they never reach 100%. From the studies it also becomes clear that a distinction should be made between gender role behavior and gender identity. Put in a broader theoretical framework, there is now more evidence that biological factors influence the development of gender role behavior than gender identity. Developmental psychology studies add evidence that social and psychological factors play a role as well in gender development. Clinicians should be aware of, but not overestimate the influences of neurobiological factors in gender development.

Teleost species from cold environments possess more disordered brain synaptic membranes than species from warm habitats, thereby providing equivalent physical structures at their respective habitat temperatures. We have related this adaptive interspecific biophysical response to the fatty acid composition of brain membranes from 17 teleost species obtained from Antarctic, temperate and semi-tropical waters, as well as from rat and turkey as representative homeotherms. Cold-adaptive increases in membrane disorder (determined by fluorescence anisotropy with diphenylhexatriene as probe) were correlated with large and linear increases in the proportion of unsaturated fatty acids, from 35 to 60 % in phosphatidylcholine (PtdCho) and from 55 to 85 % in phosphatidylethanolamine (PtdEth). For PtdCho, the cold-adaptive increase in unsaturation was associated almost entirely with increased proportions (from 7 to 40 %) of polyunsaturated fatty acids (PUFAs), with mono-unsaturates (MUFAs) providing an approximately constant proportion in all species. Exactly opposite effects were evident for phosphatidylethanolamine (PtdEth). Thus, the compositional adaptation for PtdCho occurred largely by exchange of polyunsaturated and mono-unsaturated fatty acid in the sn-2 position, whilst for PtdEth it involved exchanges between saturates and mono-unsaturates at the sn-1 position. This difference may be related to the different molecular shapes of the two phosphoglycerides and the need to maintain the balance between bilayer-stabilising and -destabilising tendencies. This comparative study provides a more comprehensive view of the compositional adjustments that accompany and perhaps account for temperature-adaptive interspecific differences in membrane physical structure.

Objective: To assess the impact of the colour of a drug's formulation on its perceived effect and its effectiveness and to examine whether antidepressant drugs available in the Netherlands are different in colour from hypnotic, sedative, and anxiolytic drugs., Design: Systematic review of 12 published studies. Six studies examined the perceived action of different coloured drugs and six the influence of the colour of a drug on its effectiveness. The colours of samples of 49 drugs affecting the central nervous system were assessed using a colour atlas., Main Outcome Measures: Perceived stimulant action versus perceived depressant action of colour of drugs; the trials that assessed the effect of drugs in different colours were done in patients with different diseases and had different outcome measures., Results: The studies on perceived action of coloured drugs showed that red, yellow, and orange are associated with a stimulant effect, while blue and green are related to a tranquillising effect. The trials that assessed the impact of the colour of drugs on their effectiveness showed inconsistent differences between colours. The quality of the methods of these trials was variable. Hypnotic, sedative, and anxiolytic drugs were more likely than antidepressants to be green, blue, or purple., Conclusions: Colours affect the perceived action of a drug and seem to influence the effectiveness of a drug. Moreover, a relation exists between the colouring of drugs that affect the central nervous system and the indications for which they are used. Research contributing to a better understanding of the effect of the colour of drugs is warranted.

Obsessive compulsive disorder (OCD) is a chronic condition characterized by an array of intrusive, upsetting thoughts and interfering, repetitive behaviors. Some forms of OCD may be etiologically related to Tourette's syndrome (TS). This cross-sectional study examines a range of obsessive compulsive (OC) symptoms which have been hypothesized to distinguish tic-related OCD from non-tic-related OCD. One hundred and seventy-seven patients with a primary DSM-IIIR diagnosis of OCD, aged 16 to 72, participated in the study. Patients with tic-related OCD (n = 56) reported more OC symptoms, including more aggressive, religious, and sexual obsessions as well as checking, counting, ordering, touching, and boarding compulsions than did patients with non-tic-related OCD (n = 121). Contrary to our expectation, these two groups of OCD patients did not differ with regard to the presence of "just right" phenomena or symptoms of psychasthenia. "Just right" phenomena and symptoms of psychasthenia, however, were both found to be associated with the current severity of OC symptoms.

In Antarctic notothenioid fishes large amounts (3% w/v) of small molecular weights of 2,600-23,500 and would be expected to be filtered into the urine, they remain in the blood because the kidneys of these fishes contain only aglomerular nephrons. Unlike the situation in most fishes, urine formation is the result of secretion rather than filtration and reabsorption. On the other hand, the peptide antifreezes in Northern Hemisphere fishes such as the winter flounder. Pseudopleuronectes americanus, are retained by the glomerular kidney even though inulin, of comparable weight, is rapidly filtered from the blood into the urine. The Antarctic eelpout (zoarcid), Rhigophila dearborni, which is unrelated to either the Antarctic notothenioids or P. americanus, also uses a peptide antifreeze (molecular weight 6,000) which is maintained at a concentration of 3% (w/v) in the blood plasma. We report here that the lack of antifreeze in the urine of R. dearborni probably reflects the fact that the glomeruli are not functional and cannot filter. We support this conclusion with morphological and physiological evidence and relate our findings to the conservation of biological antifreeze necessary for life in ice-laden polar waters.

Asialoglycoproteins injected into the tail vein of mice accumulated rapidly in the liver, as found in rats and rabbits by other authors, whereas the native glycoprotein remained in the serum for much longer periods of time. Histological examination of liver sections after the injection of radiolabelled asialoglycoproteins failed to show any binding to the hepatocyte membrane. However, silver grains were observed in the sinuses of the liver and often appeared to be bound to the sinus wall. In addition, small amounts of label in the reticulo-endothelial system of the spleen were observed. A comparison in the uptake of asialoglycoproteins by the liver, between those with alkali-labile galactose-containing (AL) chains and those with alkali-stable galactose-containing (AS) chains, showed that the former were taken up more slowly. There was no correlation between total galactose content and rate of hepatic uptake. Asialoglycoproteins with AS chains could not inhibit the uptake in the liver of those with AL chains. However, when the order was reversed, the uptake of AS containing asialoglycoproteins was inhibited by 50%. Different mechanisms to explain these results are discussed.